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Protocol Details

Phase I/II Trial of Pembrolizumab, Lenvatinib and IL-15 Superagonist N-803 in Combination with HER2 Targeting Autologous Dendritic Cell (AdHER2DC) Vaccine in Participants with Advanced or Metastatic Endometrial Cancer (EC)

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

001557-C

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Recruitment has not started
Gender: Male & Female
Min Age: 18 Years
Max Age: 120 Years

Referral Letter Required

No

Population Exclusion(s)

Children;
Fetuses;
Neonates;
Pregnant Women

Keywords

Cancer Vaccine;
Combination of anti-cancer drugs;
Immunotherapy;
HER2 Positive Cancer

Recruitment Keyword(s)

None

Condition(s)

Endometrial Cancer;
Cancer of Endometrium;
Carcinoma of Endometrium;
Endometrial Carcinoma

Investigational Drug(s)

Ad5f35HER2ECTM transduced autologous dendritic cell vaccine
N-803

Investigational Device(s)

None

Intervention(s)

Biological/Vaccine: AdHER2DC vaccine
Biological/Vaccine: Pembrolizumab
Biological/Vaccine: N-803
Drug: Lenvatinib
Device: PATHWAY HER2 (4B5) assay

Supporting Site

National Cancer Institute

Background:

Endometrial cancer (EC) of the uterus is becoming more common in the US. Sometimes EC often has increased levels of a protein called HER2. Cancers with HER2 tend to be more aggressive and have poorer outcomes.

Objective:

To test 2 study drugs-a vaccine that targets HER2 (AdHER2DC) plus a drug that supercharges immune cells that kill tumor cells (N-803)-combined with 2 FDA-approved cancer treatment drugs in people with EC.

Eligibility:

Adults aged 18 and older with HER2-positive EC that returned or got worse after treatment.

Design:

AdHER2DC vaccine is made from each participant s own blood. Participants will undergo apheresis: Blood is removed from the body through a tube attached to a needle. The blood passes through a machine that separates out the target cells. The remaining blood is returned to the body through a second needle. A special catheter may be needed.

The first treatment cycle is 28 days; each cycle after that will be 21 days.

All participants will get the 2 approved drugs and the vaccine. One drug is a tablet taken by mouth once a day, every day. The other drug is given through a tube attached to a needle inserted into a vein.

The vaccine is injected under the skin. Participants will receive the vaccine on day 1 of cycles 1, 2, and 3. Additional doses up to 3 doses will be give if possible.

Some participants will receive N-803. This drug is injected under the skin of the abdomen on day 1 of each cycle.

Treatment may last up to 1 year. Follow-up visits will continue up to 2 more years.

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Eligibility

INCLUSION CRITERIA:

- Histologically confirmed endometrial cancer

- Radiographically confirmed metastatic or locally advanced disease

- Evaluable (measurable or non-measurable) disease, per RECIST 1.1

- HER2 IHC 1+, 2+ or 3+ tumor confirmed by PATHWAY HER2 (4B5) test. NOTE: The HER2 status in participants who had prior anti-HER2 therapy should be confirmed in the tumor tissue obtained after completing the anti-HER2 therapy

- Participants must have received and progressed after at least one (1) line of systemic therapy for endometrial cancer

- Age >=18 years

- ECOG performance status <=2

- Participants must have available tumor tissue or be willing to undergo a mandatory research biopsy. NOTE: Samples must be collected after HER2 directed therapy if the participant had anti-HER2 therapy

- Participants must have adequate organ and marrow function as defined below:

-- Absolute neutrophil count (ANC) > 1,000/microliter

-- Platelets > 100,000/microliter

-- Hemoglobin (Hgb) > 9 g/dL (any number of transfusions within 60 days before apheresis is allowed)

-- Total bilirubin <=1.5 X upper limit of normal (ULN). NOTE: In participants with Gilbert s Syndrome or known liver metastasis, total bilirubin <=3.0 X ULN is allowed

-- Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) <=3.0 X ULN. NOTE: AST/ALT <=5.0 X ULN is allowed in participants with known liver metastasis

-- An estimated creatinine clearance (CrCl) <=1.5 X ULN OR >30 mL/min/1.73 m2 for participants with creatinine levels >1.5 X ULN (calculated creatinine clearance (CrCl) (eGFR may also be used in place of CrCl)

-- Dip stick urine protein < 3 or urine protein < 1 gram (g)/24 hour if dip stick urine is >= 3+

- Hepatitis B virus (HBV)-infected participants can be enrolled if HBV DNA is undetectable. Hepatitis C virus (HCV)-infected participants can be enrolled if HCV RNA level is undetectable

- Syphilis-infected participants can be enrolled if no signs of active infection as determined by an infectious disease specialist

- Participants with previously treated non-active brain metastases or central nervous system metastases more than 28 days from definitive radiotherapy or surgery are eligible

- Women of child-bearing potential (WOCBP) must agree to use highly effective contraception (hormonal, intrauterine device (IUD), tube ligation, a partner has had the previous vasectomy, abstinence) at the time of study entry, for the duration of study treatment, and up to 6 months after the last dose of the study drug(s)

- Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 6 months after the last dose of the study drug(s)

- Participants must be able to understand and be willing to sign a written informed consent document

EXCLUSION CRITERIA

- Prior administration of any standard of care or investigational checkpoint inhibitors (e.g., anti-CTLA, anti-PD-1, anti-PD-L1, anti-TIGIT, anti-TIM3, or anti-LAG3 antibodies or small molecules)

- History of severe immediate hypersensitivity reaction to compounds similar to study drugs or their components (e.g., monoclonal antibody preparations)

- Surgery to abdomen/pelvis/chest within 3 months prior to apheresis

- Other malignancies diagnosed within 24 months prior to apheresis. NOTE: Participants who completed treatment for in-situ carcinomas (e.g., breast, cervix, bladder), or basal or squamous cell carcinoma of the skin are eligible if no ongoing treatment is needed per Standard of Care

- Arterial or venous thromboembolism within 6 months prior to apheresis

- History of cerebrovascular accident or stroke (transient ischemic attack, hemorrhagic or ischemic) within 6 months prior to apheresis

- Functional or objective cardiac dysfunction: New York Heart Association (NYHA) Functional Capacity III or IV or Objective Assessment C or D

- Fridericia's corrected QT interval (QTcF) >= 480 msec or evidence of third-degree AV block on screening electrocardiogram (ECG)

- Ejection fraction by screening echocardiogram < 50%

- Participants requiring therapeutic anticoagulation regimen(s) (e.g., warfarin, rivaroxaban, apixaban, dabigatran, edoxaban, low molecular weight heparin [e.g., enoxaparin, dalteparin, tinzaparin], heparin, fondaparinux)

- History of gastrointestinal or non-gastrointestinal fistula >= Grade 3 (CTCAE v.5)

- Radiographic evidence of major blood vessel invasion/infiltration

- History of hemoptysis or tumor bleeding within 1 month prior to apheresis

- Current gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib

- Any form of primary immunodeficiency

- Participants with active autoimmune disease or a history of autoimmune disease, which require immune suppressive treatment such as systemic corticosteroids or other systemic immune suppressants (e.g., methotrexate, cyclosporine, and biologics). NOTE: Participants with vitiligo, endocrine deficiencies on replacement dose are eligible

- Systemic corticosteroid therapy of higher than a physiologic dose (the equivalent of prednisone 10 mg/day) within 14 days prior to apheresis. NOTE: Any topical steroid medications (e.g., corticosteroid creams, ointments, and eye drops) are allowed

- Solid organ or allogeneic hematopoietic stem cell transplant recipients

- Human immunodeficiency virus (HIV)-positive participants

- Pregnancy (confirmed with beta-Human chorionic gonadotropin (HCG) serum or urine pregnancy test performed in WOCBP at screening)

- Uncontrolled intercurrent illness or situation that would limit compliance with study requirements.


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Citations:

Konecny GE, Santos L, Winterhoff B, Hatmal M, Keeney GL, Mariani A, Jones M, Neuper C, Thomas B, Muderspach L, Riehle D, Wang HJ, Dowdy S, Podratz KC, Press MF. HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer. Br J Cancer. 2009 Jan 13;100(1):89-95. doi: 10.1038/sj.bjc.6604814. Epub 2008 Dec 16. PMID: 19088718; PMCID: PMC2634683.

Makker V, Colombo N, Casado Herr(SqrRoot)(Degree)ez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D; Study 309 KEYNOTE-775 Investigators. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N Engl J Med. 2022 Feb 3;386(5):437-448. doi: 10.1056/NEJMoa2108330. Epub 2022 Jan 19. PMID: 35045221.

Constantine GD, Kessler G, Graham S, Goldstein SR. Increased Incidence of Endometrial Cancer Following the Women's Health Initiative: An Assessment of Risk Factors. J Womens Health (Larchmt). 2019 Feb;28(2):237-243. doi: 10.1089/jwh.2018.6956. Epub 2018 Nov 28. PMID: 30484734; PMCID: PMC6390656.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Hoyoung M. Maeng, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CLINICAL CENTER BG RM 3B37
10 CENTER DR
BETHESDA MD 20892
(240) 781-3253
hoyoung.maeng@nih.gov

Marissa B. Mallek, R.N.
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 13N254
10 Center Drive
Bethesda, Maryland 20892
(240) 760-7498
marissa.mallek@nih.gov

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
1-888-NCI-1937

Clinical Trials Number:

NCT06253494

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